All right, great. Thank you for joining. My name is Frank Brisebois. I'm one of the biotech analysts at Oppenheimer. Our next presenting company here is Aldeyra Therapeutics. From the company, we have CEO Todd Brady to join. I think what we're going to do here, Todd, is we'll just do fireside in terms of format. So feel free to, the ones listening in, to send a question in the Q&A tab. If not, you can email me directly. And with that, thank you very much, Todd, for joining. And maybe if we can, you know, give us a little background on Aldeyra, whether, you know, is this an ophthalmology play or an I&I play? This is a loaded question right there. Frank, thanks for hosting us. We're longtime friends of Oppenheimer and longtime friends of yours, so we appreciate your interest in having us on today, well, you know, this question is, are we an eye company or are we an I&I company? Spelled differently, has come up a lot recently, and I feel like our lead program, which is in dry eye disease, has dominated the discourse on Aldeyra for so many years. It's all about dry eye. This phase III, that phase III, the NDA submission, the NDA resubmission, AbbVie, the partnership with AbbVie. I tell people that for Aldeyra, there's a near-term investment thesis, and then there's a long-term investment thesis, well, the near-term investment thesis is around dry eye disease. We have a PDUFA date on April the 2nd, so coming right up. We have an option deal with AbbVie, which is the largest company by a lot in eye care, particularly the front of the eye, which involves a $100 million exercise fee less what they've already paid us, which was $6 million, plus a $100 million milestone on approval, plus a couple hundred million other milestones, plus a 60/40 P&L split, so I think in terms of near-term investment thesis, not only do we have a PDUFA, but the PDUFA is tied to a tremendous front of the eye deal, probably the biggest front of the eye deal ever in terms of license and/or profit split kind of arrangements, and then the long-term thesis is about I&I. It's about immunology. And for so many years, as you know, Frank, I've been describing Aldeyra as an immunology company, which is really sort of what dry eye is. It's an immunological disease characterized by redness and pain and other kinds of signs and symptoms of inflammation. It turns out our drug is probably active in other ways, like vasomotor control and acute neurosensory control. Be that as it may, I think that the pipeline is focused on immunology. So atopic dermatitis, the inflammatory aspects of dry AMD and geographic atrophy, metabolic inflammation, which includes hepatic inflammation and obesity and pain and substance abuse and all the other things that sort of are comorbid with eating too much food. These are really the indications that represent the future of Aldeyra. So I would say in short, the near term is about the eye. The long term is about the eye plus other parts of the body that have to do with inflammation. Okay. And I think, you know, as much as, you know, it's impossible to avoid talking about the dry eye program, especially because this is not just a small deal, as you mentioned, and the PDUFA is very, very close. So actually, this is a different type of question. Because of the CRL, and it seems pretty straightforward, you guys had new data, you submitted the data. Is this fair to assume that is there a chance here that this happens before the PDUFA, or it's just so hard to tell at this point? You mean the AbbVie relationship? I mean the approval, you know, like they give a PDUFA. Oh, yeah. And then, can the PDUFA of April 2nd come early or not just because of how straight, you know, or is this something we can't comment on? You know, another way of asking that question is, what's taken them so long? Yeah. You know, so just to back up and for the listening audience, we submitted our first NDA for dry eye disease at the end of 2022. That review was 12 months. At the end of 2023, we got a complete response letter. In dry eye disease, there are 4 clinical trials that companies do, right? Not 2, but 4. 2 for signs, which are something that an investigator can judge. In our case, that's redness. A very relevant sign to all of us, redness, ocular redness. And 2 are symptoms, which is how do you feel? That's reported by the patient. And one of the symptom trials, according to the FDA, needed to be repeated for various reasons. And so we repeated that trial last year. We resubmitted the NDA in October, PDUFA date in April of this year. The trial that was resubmitted based on a special protocol assessment type A meeting and other things that we had back and forth with the FDA, you know, was roughly 120 patients or so, and it was a dry eye chamber trial, which is cool because dry eye disease is about flares. It's not like every day you're a 7 out of a 10 in pain. It's some days you're a 9 and some days you're a 2, so this dry eye chamber concept, which is in FDA draft guidance, I encourage you to go look it up. It's right there, is really designed to simulate these flares, which are characteristic of dry eye disease. It's a very short trial, by and large. It's 100 minutes in our case. So you've got, let's just call it round numbers, 100 patients. You've got 100 minutes of testing, one trial to satisfy the CRL. It seems like a pretty straightforward exercise. On the other hand, there are other things that are involved in NDA resubmissions, such as a new draft label, an updated safety database, the clinical trial data. You know, there are a few other things like CMC updates for stability, which is always ongoing. I think you run stability for 3 years. So there's all these kinds of things that the FDA looks at. I'm not sure the current administration is helping the FDA in terms of staffing and funding. And so my expectation, just playing the odds, Frank, is that the PDUFA will come, the decision will come right around the PDUFA date, April 2nd. Okay. And I think, you know, I've covered, I've looked at dry eye companies for a while here. You just discussed the redness that you used here as a sign. Can you just help us understand maybe how Reproxalap is differentiated and why did you take redness and discomfort? And just talk about the signs and symptoms that are chosen here. The signs for dry eye disease, which are again in that draft guidance document from the FDA, are many-fold. I mean, there's tear osmolarity. There is Schirmer test, which is a piece of paper in the eye that measures the amount of fluid in your eye. There is corneal staining, which is a drop of dye on the front of your eye. Many of you probably had it done. You have the slit lamp, this vertical line that goes back and forth, and you look for defects in the corneal epithelium, but the only one that we care about as patients and as humans is really redness because none of us want to have a red eye. A lot of dry eye patients will complain about how their colleagues think they're on drugs, and the reason is their eyes are always red or bloodshot. And that is just not something that anyone wants. So I like to say that redness is the only sign that patients care about in a sense, and probably often is. I mean, who wakes up and thinks, "I wonder what my staining score is today?" Instead, you wake up and you look at yourself in the mirror, especially at my age, and you think, "God, my eyes are red. I look terrible." So we're thrilled. And I think in theory, AbbVie is thrilled to have redness on the label. And the biggest thing, I think, redness is important, but the biggest thing that, you know, there's a company that's tried to do speed of onset with the steroid. Obviously, steroid has its own baggage. But can you just talk about what are these chamber trials for those that aren't as aware, you know, familiar with them? I think in allergic conjunctivitis, it's been known in the past a little bit more. But in dry eye, what are these chamber trials and how did, you know, what kind of speed of onset did you get to see here? In both dry eye and allergy, you can run chamber trials. And that's no accident. Because again, I didn't really talk about allergy yet, but allergic conjunctivitis. But, you know, this is a disease of flares. And if you have allergic conjunctivitis like I do, your flare season is spring and fall. That's when there is pollen. Both allergy and dry eye related. I mean, I think about half the patients that have dryness complain of itching, which is sort of the characteristic symptom of allergy. And half the patients that have allergy or itching complain of dryness. So they're probably part of the same disease, but on a different spectrum. We know that pollen exacerbates dry eye, for example. We know the drugs you take for allergy, antihistamines, make your eye drier. So there really is this intimate relationship between the two. You mentioned steroids. Steroids are interesting for 2 reasons. One, it's the only drug for dry eye disease that has redness on the label. The problem is toxicity. It also says on the label, you can use this for 2 weeks and that's it. Because after 2 weeks, you increase the risk of glaucoma or the risk of cataracts. I think the other reason steroids are interesting is because they're also indicated for allergy. It's sort of this anti-inflammatory. Steroids are a hammer, right? They're a broad-based anti-inflammatory approach. The problem with hammers is sometimes you damage the things you don't want to affect. And that's certainly the case with steroids, certainly after 2 weeks of therapy. That's why they're limited to acute use only. Reproxalap, in theory, would be the only drug indicated for chronic use for both diseases. And that's really quite amazing. So the idea would be if Reproxalap is approved for dry eye, either Aldeyra or AbbVie would submit a supplemental NDA for allergy. You know, in our corporate deck, we have what we believe are our 2 pivotal trials, phase III trials for allergy. They're in an allergen chamber, not a dry eye chamber. The endpoints are itching instead of discomfort and dryness. They're itching and then redness. So both dry eye, in our case, both dry eye trials and allergic conjunctivitis trials look at redness. And again, we talked about the importance of that to patients. But for both diseases, redness is a big issue. Did you mention here how quickly are you seeing an effect based on the chamber trial? The chamber is 100 minutes. In allergy for dry eye, in allergy, it's longer. It's about two and a half hours or so. You know, if you look at the data in our deck, the first time point we assess is at 10 minutes after entering a chamber. It's hard to assess time points before that because patients are getting in. It's sort of this noxious experience. I mean, I can't imagine doing it. But it's, you know, it's like sitting on an airplane with those vents, those little air things, you know, aimed right at your eyes and keeping them open while you fly across the country watching a movie, except with no humidity. And so it's a very noxious experience. So assessing outcomes before 10 minutes is sort of difficult. Patients are getting used to it. They're, you know, after 10 minutes, they probably stop freaking out as much, and then you can look, but at 10 minutes, you see a difference, and I often get asked, "Why is there a difference at 10 minutes?" I mean, it's just 10 minutes, and people are just ramping up in terms of their symptoms and signs in that chamber, and the answer is we dose right before the chamber, so there is that pre-chamber dose, which was designed originally to measure prophylaxis or prevention. Can we prevent this exacerbation of signs and symptoms either in dry or allergy in the chamber? The other reason is the day before the chamber, we dose the drug as well, and the reason for that is to familiarize patients with dosing. And you don't want to have a technician stick something in your eye 5 minutes before going into a dry eye chamber. So you familiarize them with the technician dosing drug and so forth. And that really, that said, it's kind of habituation process or familiarization process is important so the patients aren't upset as they enter one of these dry eye or allergy chambers. And that pre-dosing really, I think, predicts or explains that difference you see at the first time point in the chamber where drug is not as bad as vehicle where patients are really escalating. Okay, great. And then just to kind of close up on dry eye, the AbbVie agreement, you mentioned a lot of numbers at the start of the call, but just, you know, they're pretty significant numbers here. Can you just mention them one more time in terms of the deal, what it means, and the timing on which you expect some of these numbers to kick in here if the option is exercised? Right. I always tell enthusiastic investors that all these agreements are filed. They are public. They're exhibits to our 10-K or subsequent exhibits. Some of the details are redacted for obvious reasons, but by and large, the salient information is disclosed. There's a wonderful summary in our corporate deck of these deals. It is AbbVie has an exclusive option on essentially anything in the front of the eye and everything with Reproxalap. Okay, and that option is $100 million upfront. Now, to enter into the option and extend the option, they've already paid us $6 million of that $100. So if AbbVie chooses to exercise the option, it's $94 million upfront at this point, plus the $6 they've already given us. If the drug is approved, it's an additional $100 million. So in the event that AbbVie chooses to exercise after the drug is approved, and they have 10 business days from approval to the expiry of the option, if they choose to exercise during that 10 business day period, it's $194 million paid all at once. There are $200 million in other milestones. So there's a $100 million milestone and an additional $100 million milestone in the future. The nature of those milestones isn't disclosed. And then there is a 60/40 P&L split, which means that Aldeyra pays 40% of the costs and shares in 40% of the profits. We are capped on a yearly basis in cost. In other words, there's a limit above which we don't need to pay that year. That excess above that limit is deferred against future profit. And the reason for that is, you know, large pharmaceutical companies can often spend a lot of money, 40% of which small companies may not be able to spend. That's definitely not the case here because of the cap and the size of the milestones we've discussed. So I think, you know, your typical time to profitability for any drug is 3 to 5 years. In dry eye, I think it's a little bit shorter, just given the nature of the space, probably the size of AbbVie, the commercial reach of AbbVie, not only in ophthalmology, but also optometry. Optometry is responsible for about 60% of the dry eye scripts. So obviously, very near future, that is within 5 years, we're super excited about in terms of the financial implications of the deal should AbbVie choose to exercise and should the drug get approved. Okay. Okay, great. And just on that note, you talked about a lot of cash here coming in. Where do you guys stand as of the last reporting? Just over $100 million. The 10-K will come out soon. I don't think you'll see any surprises there. We're a very efficient company in terms of burn, in terms of number of employees. We outsource very effectively. We spend a lot of money, but at the same time, we have financial flexibility in terms of the amount of cash we have and the fixed cost we have internally. Our current guidance is cash through 2026, and that excludes any contribution from AbbVie. It excludes any revenue. It excludes all these kinds of things that are at this point to be worked out or contingent. And AbbVie was kind of the original Allergan on the dry eye side with Restasis. Can you just help us understand what how are the scripts doing now? What's the dry market now? Is it mostly generic? What's out there? And just what are you trying to compete with here? You and I are old enough to remember those Allergan days and the Restasis days. You know, my father is retired now. He was a neurologist. But he asked me, he said, one day, he said, "What are you working on?" And I said, "Dry eye disease." And he said, "Is that a disease?" And I said, "Yeah, Dad, it's a disease." And Allergan invented that disease in a sense, right? I mean, there's about 40 million people in the U.S. that have some form of dry eye, and that's increasing. And the reason it's increasing in my mind is probably two or threefold. 1 is we're all getting older. Our eyes dry out as we're getting older. 2 is we're looking at screens like we're doing right now. And 3 is pollution and/or global warming causing more pollen. Those are sort of the big 3 that lead to this increase in dry eye. It's not going to go away, and it's not going to get better, and so we need new therapies, and kudos to Allergan for developing cyclosporine as a topical eye drop and a form of Restasis. I think they launched that drug in the sort of the 2006, 2010 timeframe. It was $1.5 billion at peak. It's still, if you combine the brand with generics, is probably the top-selling dry eye agent, but that was all done by Allergan and now owned by AbbVie, so if there's a group we want to work with, it's the folks that sort of invented this space in a sense that first commercialized this space. There's no company that knows more about dry eye disease than AbbVie. Restasis went generic, I don't know, a few years ago. It was difficult to formulate for generics. The actual eye drop suspension is kind of an interesting CMC challenge. And so finally, generics came about. The sales continue to erode, as you'd expect when generics enter the market. I think that's good for Aldeyra, though, because that means that AbbVie is probably interested in bringing on a substitute for Restasis as sales continue to decline. And EyeCare, I tell people, is one of the 5 therapeutic pillars of AbbVie. It may not be the biggest, but it's still one of the therapeutic pillars. Okay. And then can you talk about your push in the back of the eye? Right. I used to say that we start in the front, we metastasize to the back, and then we're going down through the rest of the body. To some extent, that's true. Our platform is based on a novel target called RASP, which is a, I tell people, it's sort of like a small molecule cytokine, except there's a whole bunch of different ones. And our small molecule therapeutic is a little bit like an antibody, except it's a small molecule. It binds up all the RASP. I really enjoy reading about all this I&I emphasis on depletion now. You know, we're depleting B cells. We're depleting T cells. Well, we're depleting RASP at Aldeyra. Maybe I should stop calling them RASP modulators and instead call them RASP depleters. RASP are a problem in dry AMD. So of the 2 naturally occurring RASP in the body, one is vitamin A. It's called retinaldehyde. Retinaldehyde is fine. It helps you see. It's critical to help you see. But as we get older, our ability to keep retinaldehyde in check within the right correct biochemical pathways degrades. And then retinaldehyde escapes and binds to things and forms these metabolites in the back of the eye. They're part of drusen, which accumulate in dry AMD. The other thing about retinaldehyde adducts is they degrade your ability to see at night, so-called night blindness. And as we all get older, it's harder to see at night. And that's one reason why is that we have unchecked retinaldehyde binding the back of the eye. Well, what binds retinaldehyde? Our RASP platform, our RASP modulator platform. And so that's something that really was integral in the founding of Aldeyra back in the early 2000s. We're getting back around to the retina. I can't wait to see what these compounds do when injected into the eye in dry AMD patients. This is literally the first symptom that dry AMD patients complain about is, "I can't see at night. I trip over my dog at night. I trip over my slippers. You know, I can't drive as well at night." I was just talking to a woman who's looking at dating again in her 80s. And she said her main criterion was drive at night, right? So it is just hard to do as you get older. Well, you know, today we treat dry AMD by reducing lesions. Patients don't care about lesions. Patients care about how well they see, how well they function. And that's exactly the kind of endpoint that I think we're going to start looking at, hopefully by the end of this year in the clinic. Okay. So that's that in terms of stage, that's hopefully by the end of this year in the clinic. And then what about RP? RP is the subject. Retinitis pigmentosa is one of the most common orphan eye diseases. Orphan is fewer than 200,000 patients in the U.S., so it's orphan, and there is really no therapy. There's one drug called Luxturna, which treats a very small number of retinitis pigmentosa patients. One of our key opinion leaders in retinitis pigmentosa has never treated a patient with Luxturna, so there is really no therapy for the bulk of these patients. This is a progressive loss in vision due to a series of genetic mutations that lead to degradation of your photoreceptors. That is the cells in your retina that sense light, so we're thrilled to be working in the space. It turns out that ADX-2191 is an intravitreal formulation of methotrexate. Vitreous is the stuff in the back of your eye. Intravitreal means injection to the eye. And we ran a phase 2A trial open label just with methotrexate treatment. Last year, the data were fantastic. I mean, patients all get better versus baseline. Now, we didn't run a control. So the next step is to run what we hope is a potentially pivotal trial, phase II, III trial, where some patients get a methotrexate, maybe a high dose or a low dose. Maybe we'll have a control. And so then we can see really how active methotrexate is. We're hoping to get that trial going later this year. It's a 12-month treatment paradigm. So it'll take a while. It's a rare disease, long treatment. But I really do think from the patient's perspective, there could be a pot of gold at the end of the rainbow, just given that there's nothing to treat this progressive loss of vision today. Okay. And what kind of control would that be? Todd, this is a subject of debate with many companies and the FDA. Typically, the FDA asks for a high dose and a low dose. Okay. You're comparing a high dose to a low dose. The issue is you can't inject saline, can't inject a placebo because there's risks to injection, which include infection or retinal detachment and so forth. The debate with many companies and the agency, and I would say including ours prior to getting the trial started, is what kind of control other than a very low dose of drug can we use? I think you'll hear from us shortly on the final trial design before it gets started. Okay. And then lastly, we talked about the eye. We're going down, I guess, maybe derm and then liver, I guess. That's right. I know. Yeah. I know. Yeah. Yeah. So atopic dermatitis is my most frequent inbound outside of dry eye. And the reason for that is we have an oral program, ADX-248. It's in phase I. I'm happy to say it's going very well at this point. We have excellent exposure to drug. This is a very potent molecule. It appears at this point we'll have a once-a-day molecule pending the completion of phase I. Well, I remember, you know, decades ago, I was looking at a website for a large pharmaceutical company, and they said, "What we really want is a once-a-day pill." That was sort of the headline on their business development website. I think that's what we have here with 248. We'll see. We'll get through phase I. We'll unblind. We'll see who's on placebo, who's on drug. We'll confirm the drug levels we're seeing. But at this point, I think we're making great progress towards a once-a-day pill with ADX-248. The reason I mention all that is because a lot of atopic dermatitis is in kids. And most of it, like any other disease, is mild to moderate. So who wants to take injections? Who wants to, especially if you're a child, administer Dupixent every month? Who wants to risk the toxicity associated with some of those drugs, especially mild to moderate, or you're a kid? So a pristine safety profile with a once-a-day pill could be something of great interest to a lot of patients in atopic dermatitis. And that's sort of where we're aiming. Okay. Great. And then just to close out, do you want to touch on alcoholic hepatitis? Right. And metabolic inflammation. We used to say obesity. Now we say metabolic inflammation. Metabolic inflammation is not just obesity. It's sort of this old metabolic syndrome concept where you're overweight, you have hepatic inflammation, your lipids are out, dyslipidemia, hypertriglyceridemia, you have pain, you have substance abuse, all the things that you see GLP-1 trials in today. That's sort of where we're going. It turns out RASP are precursors of triglycerides. To make a triglyceride, you need a fatty acid. To make a fatty acid, you need a fatty aldehyde. And those are RASP. Those are pro-inflammatory. I think the more we learn about obesity and metabolic syndrome, it's an inflammatory disease. So I put metabolic inflammation squarely under I& I. And I think companies that are not thinking as much about obesity or metabolism today, but do have an I&I program, are going to learn how to fit metabolism in there because ultimately, we're just getting more inflamed as we eat more for a whole bunch of reasons. And so I think what you'll hear about possibly is a clinical trial plan that involves obesity and hypertriglyceridemia, all the things I mentioned, pain, substance abuse, and so forth, where we've demonstrated some activity either clinically or preclinically with our RASP platform in the past. I think that wraps it up in terms of time. Is there anything else I should have asked that we didn't get a chance to talk about? Excited to be here, Frank. As always, thanks for hosting. Great. All right. Thank you. Thanks everyone.